Sensitivity of rat soleus muscle to a mechanical stimulus is decreased following hindlimb unweighting.

Mechanical loading is thought to be an important stimulus regulating muscle mass. However, the responsiveness of a muscle atrophied by a period of mechanical unloading to a subsequently imposed mechanical challenge is not well understood. This study examined the phosphorylation of the mechanically sensitive p54 c-jun NH(2)-terminal kinase (JNK) signaling protein in atrophied rat soleus muscle in response to a mechanical challenge in situ (isometric contractions; 100 Hz, 150 ms, once every 1 s for 5 min). Rats underwent either 7 or 14 days of hindlimb suspension (HLS) following which phosphorylation of JNK was measured biochemically. Immunofluorescence analysis revealed that phosphorylated JNK was localized in myonuclei. Baseline JNK phosphorylation measured in non-stimulated soleus muscles of 7- and 14-day HLS groups was 3.0- and 2.8-fold, respectively, the baseline phosphorylation measured in muscle of weight-bearing control animals (CTL). Following a mechanical challenge, JNK phosphorylation in stimulated CTL and 7-day HLS groups was significantly increased by 3.2- and 1.8-fold at the non-stimulated baseline levels, respectively. In stimulated muscle of 14-day HLS, JNK phosphorylation levels did not significantly differ from the baseline levels suggesting that the ability to elicit a mechanically induced phosphorylation of the JNK signaling protein gradually decreases with unweighting and is attenuated after 14-day HLS. Changes in the responsiveness of mechanically sensitive intracellular signaling pathways in atrophic muscle may contribute to the functional impairment experienced by muscle in the absence of weight bearing for prolonged periods.